1. Field of the Invention
The invention concerns a device and a process for directed and specific manipulation of small quantities of matter on the surface of a solid body and use thereof.
2. Description of the Related Art
Movement of small quantities of matter is performed at this point in time primarily in the field of liquids (microfluids). Thus movement of small quantities of liquids (and at the same time suspended particles contained in them, such as biological cells) on a chip has already been used in biology (Anne Y. Fu et al., Nature Biotechnology 17 (1999), pages 1109f). To move small quantities of matter, conventional pump systems (including miniaturized pumps) are used on the one hand, that move defined quantities of liquids along defined channels by structuring solid-body surfaces. These conventional pump systems are based essentially on miniaturization of known functional units, which are driven by purely mechanical or piezoelectric actuators. In this, methods of micromechanics are used, among others, based on significant miniaturization of known pump mechanisms or known hydraulic and hydrodynamic functional blocks, such as valves, turbines, nozzles, etc. Another type of liquid transport that has arisen recently is based on utilization of electrokinetic processes, in which an electric field causes movement of a liquid along a defined channel (O. Mxc3xcller, Laborwelt 1/2000, pages 26 though 38). Movement of small liquid quantities by impulse transfer of a longitudinal volume sound wave on a liquid is known from U.S. Pat. No. 5,674,742 and from U.S. Pat. No. 6,010,316.
In electroosmotic processes, the speed of the quantities of matter to be moved depends on the channel width, as a rule. In addition, the channel must be completely filled, in principle. Also, high field strengths are required to transport small quantities of liquid, which lead, in addition to undesired electrochemical and electrobiological effects, also to an unavoidable joule heating of the quantities of matter to be moved, which can, among other things, affect the functionality of the carrier material.
The task of the present invention is to provide a device and a process, with the help of which specific manipulation and movement of the smallest quantities of matter on and along the surface of a solid body, in which the movement of the smallest quantities of matter is possible without moving parts and makes cost-favorable and simple production and use possible.
This task is accomplished by a process and device for specific and direct manipulation of small quantities of matter on solid-body surfaces in which, with the aid of one or more acoustic surface waves, an impulse is generated along the solid-body surface, with the surface wave being generated with a surface-wave generator. The impulse is made to interact with at least one quantity of matter in order to cause movement on the surface in a desired direction.
In the process according to the invention, surface waves are generated with the aid of at least one surface-wave generating device, the impulse of which is made to interact with at least one quantity of matter, in order to cause movement in a desired direction. The device according to the invention also has at least one device for generating surface waves on a solid-body surface in at least one direction of spreading and an interaction region, in which the quantity of matter can interact with the at least one surface wave, in order to cause movement of the quantity of matter through an impulse transfer by the surface wave or surface waves.
With the process according to the invention and the device according to the invention, the smallest quantities of matter on the surface of a solid body can be moved or manipulated specifically by means of acoustic surface waves. Here, the concept xe2x80x9cmatterxe2x80x9d includes gases, liquids, and solid substances, but also biological systems, such as cells, macromolecules, and genetic material, as well as small particles, such as chemical reagents or mixtures, solutions, or dispersions of these substances. At least one acoustic surface wave is generated on the surface of the solid body. Through the interaction of small particles, liquids, or gases with the periodic mechanical deformation of the surface, or also through interaction with the electric fields accompanying the wave, these particles, liquids, or gases are moved specifically. Here, the amount and direction of each speed can be set in advance externally. Transport of the matter on the surface of the solid body along a path that can be selected freely and set specifically is thus caused by an impulse transfer between an acoustic surface wave and the small quantity of matter to be transported. Manipulation or movement of the small quantities of matter on the surface of the solid body takes place without direct contact between the actual xe2x80x9cpumpxe2x80x9d and the matter to be transported, since the displacement of the matter is caused by the impulse transfer alone, which occurs, e.g., through mechanical deformation of the solid-body surface or also through electric forces, transmitted through the piezoelectric fields accompanying the surface wave. In addition, at at least one point on the solid-body surface, a corresponding sound converter or a surface-wave generator is prepared, through which a high-frequency acoustic surface wave can be excited along the surface of the solid body.
Matter transport through impulse transfer from a surface wave permits high current and process speeds with comparatively small electric field strengths up to the speed of sound for surface waves on the corresponding substrate. Moreover, the process presented can be scaled over broad ranges, since the speed of the quantity of matter to be moved does not depend on the channel width, as it does, e.g., in the electroosmotic process. In contrast to, e.g., the electroosmotic transport process, no high field strengths are needed for transport that could possibly lead to undesired electrophysical or electrochemical reactions. The small quantities of matter to be transported are located, disregarding any high-frequency alternating field that may be present accompanying the surface wave, in a field-free space. Especially for biological systems, such as cells, damaging effects of high electric fields are thus avoided. The method of functioning of the pump mechanism is independent of the type and properties of a transport or buffer liquid that may be used. In addition, with the process according to the invention, undesired joule heating is avoided.
Since both the direction of the effectively acting surface wave or surface waves on the solid-body surface, as well as their position and amplitude can be set as desired and separately, it is possible to set the transport speed specifically with respect to amount and direction. Thus it is possible to define complex transport segments and paths for small quantities of matter on the solid-body surface.
The surface wave can be generated either continuously or in pulse form.
Finally, it is not necessary, e.g. with closed fluid volumes, to irradiate the entire volume with the surface wave, since because of the incompressibility of liquids, driving a small partial volume is sufficient to move the entire volume.
Another advantage of the device according to the invention is the possibility of moving individual drops, e.g. of a liquid or a buffer solution, forward. Because of surface tension, drops of this kind do not run away from each other. Small quantities of matter can thus be transported without a surrounding column of liquid.
Finally, the process according to the invention and the device according to the invention makes a very directed control of the movement mechanism possible. The surface waves runs laterally, because of the crystal properties of the substrate, * to their being generated on the surface only slightly apart from each other. In this way, a very definite effect of the surface wave on the small quantity of matter is possible, even when the direction in which the surface waves are generated is not in the immediate neighborhood of the small quantity of matter to be moved.
With the device according to the invention, construction of a xe2x80x9clab on the chipxe2x80x9d is possible. Here, a xe2x80x9cchip,xe2x80x9d such as is known, e.g., from electronics, serves as a solid-body surface or substrate. Various devices according to the invention can be combined for various purposes. Finally, one or more analysis stations can also be provided on the same chip surface, in which the quantity of matter is made to interact with an external measurement quantity, e.g. a local illumination, a local heating, a local magnetic field, an electric field, or, e.g., a local mechanical load.
In this case, the device according to the invention can be produced in a simple manner and the process according to the invention can be implemented easily.
Advantageous embodiments of the invention are objects of the subclaims.
All materials can be considered as solid bodies on which an acoustic surface wave can be generated. Especially suitable, because of their functionality, are, e.g., semiconductor surfaces.
Acoustic surface waves can be stimulated in an especially simple manner, in which case the use of piezoelectric solid-body surfaces is advantageous.
The movement device for a quantity of matter can result directly from the impulse direction of the surface wave or the impulse direction of the vector sum of the impulses of individual surface waves. It is possible, however, to provide the solid-body surface with predetermined defined trajectories, along which the quantity of matter will move. In predetermined trajectories of this kind, the direction of movement is determined by the direction of the trajectory, so that a slight angular error in the direction of the impulses of the surface waves does not damage the desired direction.
Trajectories of this kind can be achieved by grooves, barriers, lithographic definition of channels, or modulation of the wetting properties of the solid-body surface. Such structures can easily be applied to solid-body surfaces, e.g. through lithographic processes, which are well known from planar technology. By combining several regions defined in this way on the solid-body surfaces, xe2x80x9cconducting paths,xe2x80x9d mixing chambers, branches, or networks can easily be produced. The definition of a complex network of xe2x80x9cconducting pathsxe2x80x9d made in this way for matter transport on the surface of a solid body makes it possible to prepare completely functional units for physical, chemical, or biological manipulation of matter on the surface of the solid body.
In a special embodiment, functionalization of the solid-body surface is achieved by modulation of the wetting properties of the solid-body surface. This can occur, e.g., by defining hydrophobic and hydrophilic regions on the surface of the solid body, e.g. by direct coating of parts of the solid-body surfaces or by micro- or nanostructuring of certain regions of the surface of the solid body. The shape, position, and breadth of xe2x80x9cconducting pathsxe2x80x9d defined in this way can be set directly, for example by lithographic techniques. Combining these xe2x80x9cconducting pathsxe2x80x9d with regions of the solid body that have been functionalized in a similar way, which then serve as reservoirs, mixing chambers, analysis stations, or sensitized regions for sensor applications, permits a large band width of possible applications of the present invention as a xe2x80x9clab on a chip.xe2x80x9d All process steps are based on known processes of semiconductor technology, so that a specific adaptation of the chip layout can be made for a special problem or an application in a rapid and cost-favorable manner.
Definition of xe2x80x9cconducting pathsxe2x80x9d for liquids by modulation of the wetting properties of an otherwise planar surface avoids the etching of grooves. This also automatically avoids a blockage of small channels, and a cleaning of the solid-body surface that may be needed is very simple.
Because of the planar surface, sticking of the matter to be moved at corners or edges is excluded. In addition, layers could be obtained in a simple manner with known coating techniques for modulating the wetting properties.
Providing strips of relevant surface regions according to the invention with surface waves also generates an inherent cleaning effect, which simplifies additional cleaning or makes it superfluous.
The wetting behavior of xe2x80x9cconducting pathsxe2x80x9d produced in planar technology for liquids based on modulation of the wetting properties of the solid-body surface in addition to depending on to special functionalization of the surface (coating, mechanical handling, changing the composition) itself, is also sensitive to the volumes to be transported. In this way it can be achieved that certain regions along a conducting path are wetted or not along a conducting path when excess liquids are introduced. By this means, e.g. self-organizing valve functions can be realized.
With this, the quantity of matter to be moved can be kept in either hydrophobic or hydrophilic and either lipophobic or lipophilic regions according to their adhesion properties.
In another embodiment, modulation of the wetting properties is achieved by silanization of a portion of the solid-body surface. To generate a xe2x80x9cconducting pathxe2x80x9d for an aqueous solution, the surrounding region can be made hydrophobic by, e.g. silanization.
Advantageously, the acoustic surfaces are generated by electric stimulation. A simple possibility for this is offered by interdigital converters, so-called interdigital transducers. In the simplest embodiment, these consist of at least two metal structures the mesh in the manner of combs, applied in at least one planar-technology process to a substrate surface. If a high-frequency alternating-voltage signal is applied to such an interdigital structure, then a crystal deformation results according to the inverse piezoelectric effect, which has the spatial periodicity of the interdigital converter and the time periodicity of the high-frequency alternating voltage. To the extent that the applied high-frequency alternating-voltage signal is applied in resonance with the speed of sound on the surface involved, then an acoustic surface wave spreads out perpendicularly to the axis of the converter. The corresponding resonance condition is f=v/xcex, where f is the frequency of the applied alternating field, v is the speed of sound of the surface waves, and xcex is the spatial periodicity of the interdigital converter.
If the acoustic surfaces are generated by means of the piezoelectric effect, then the impulse transfer between the at least one acoustic surface wave and the at least one quantity of matter can be transmitted through the electric fields accompanying the waves in the piezoelectric substrate by transmitting electric forces to charged or polarizable matter. In another embodiment of the process, the accompanying mechanical deformation of the solid-body surface is used to transfer for impulse transfer to the quantity of matter.
The piezoelectric effect can be generated in the substrate itself if a piezoelectric substrate is used. On the other hand, the piezoelectric effect can also be used in a piezoelectric layer on the substrate surface. The piezoelectric layer can be selected in such a way that it has different wetting properties than the rest of the substrate surface. In this way, a modulation of the wetting properties can be used at the same time* to generate the piezoelectric effect to form xe2x80x9cconducting pathsxe2x80x9d.
Preferred embodiments include unweighted converters, weighted converters, monodirectionally radiating converters, focusing converters, and converters for multifrequency operation. Matter transport then occurs along the direction of spreading of the surface waves. By superimposition of several surface waves, a resultant total impulse can be set whereby the spreading of the quantity of matter does not necessarily have to occur parallel to the spreading direction of the surface waves. In addition, the frequency, amplitude, and also the phase position can be set directly with respect to another wave, in order thus to generate complex interference and superimposition patters. Thus both the quantity and also the direction of the velocity vector can be set directly for the matter transport within broad limits.
Interdigital converters can also be generated very simply with known planar-technology methods on surface-body surfaces. The represent a well-defined purely electric interface between the device and possible external guidance and control electronics. It is likewise conceivable that the necessary surface waves or pulse sequences can be controlled through the wireless radiation of a high-frequency alternating voltage. For this, e.g. an antenna device can be provided.
Converters with constant distances between fingers can be used as interdigital converters. The a uniform surface wave is sent through the entire width of the interdigital converter over the surface, when a corresponding frequency is applied.
If several interdigital converters are provided on the surface that can move or manipulate the quantity of matter in different directions, it can be achieved through suitable selection of the distances between fingers in each case that the various interdigital converters come into resonance at different frequencies. Thus the frequency of each interdigital converter can be selected and thereby the quantity of matter can be manipulated in the desired manner.
In an advantageous embodiment, it is provided that at least one interdigital converter is used with a non-constant distance between fingers for generation of surface waves of different frequencies. In this case, the surface waves are generated only at the place where the resonance condition is satisfied. Different frequencies thus lead to a stimulation of surface waves at different points of the interdigital converter. The non-constant distance between the meshing fingers of the interdigital converter can be changed, e.g. stepwise. Especially simple, however, is a so-called xe2x80x9ctaperedxe2x80x9d interdigital transducer. Here, the distance between the fingers of the interdigital converter changes continuously, e.g. linearly. As the frequency increases, the place of stimulation moves continuously along the interdigital converter. Thus the region in which the surface wave spreads can be set very precisely and a very local impulse transfer to a small quantity of matter is possible. Likes, various quantities of matter can be controlled selectively by choosing the frequency, if the axis of the interdigital transducer is kept divided, e.g. along the interdigital transducer.
By selecting complex combinations or sequences of the operating frequency, a multiplexing or switching of matter currents is possible. With only one high-frequency source that controls the transducer with non-constant distances between fingers, a number of possible paths can be programmed and set, along which acoustic surface waves move the smallest quantities of matter.
Thus specific control of the smallest quantities of matter along predetermined paths is possible using a single device, without moving parts. Thus the device can be set completely through the operating frequency and also the amplitude of the high-frequency alternating voltage applied to the transducer. With several interdigital transducers of the type mentioned, it is possible to generate complex wave fields by manipulation of the smallest quantities of matter along the surface of the substrate involved.
Here too it is possible to stimulate the generation of surface waves by wireless irradiation of a high-frequency field of a definite frequency. By selecting the frequency, the place where the surface waves are generated can be specified very precisely.
The process according to the invention for manipulating or moving a quantity of matter can be used to divide a quantity of matter into two parts by irradiating an acoustic surface wave. In this case, an acoustic surface wave is sent, e.g., to a quantity of matter at rest. By selecting parameters appropriately, parts of the quantity of matter then move away from each other. It can likewise be provided that a moving quantity of matter, moved e.g. by a device according to the invention, is divided with a surface wave sent from the side and thus divided into two subquantities.
Another embodiment of the process according to the invention makes a mixing possible, in which surface waves are sent from various directions to at least one quantity of matter. By this means, the quantity of matter can be changed in motion without changing its overall position.
In order to mix two drops of liquid, they can be moved directly toward each other by an embodiment of the process according to the invention. Two surface-wave generators, the radiating characteristics of which consist of at least two parts running at an angle of 180 degrees from each other, generate surface waves that cancel each other""s effects under normal circumstances. If, however, the surface wave in one of these generating directions encounters a first small quantity of matter, e.g. a drop of liquid, then on the one hand it transfers an impulse to it and on the other hand it is attenuated. If it then encounters another small quantity of matter, it is already weakened in its effect. Similarly, the surface wave generated by the other surface-wave generator transfers an impulse to the other quantity of matter and is attenuated. The effect of the surface waves in opposite surface-wave generating directions is thus stronger at the place of the quantity of matter than is nearer to each surface-wave generator. Thus two small quantities of matter, e.g. drops of liquids, can be driven directly toward each other in order to be mixed or for purposes of a reaction.
In another embodiment according to the invention, a surface wave is sent approximately tangentially to the at least one small quantity of matter, so that it is caused to rotate.
A device according to the invention can also include e.g. a defined trajectory with an essentially round region, whereby the at least one generating direction for surface waves is arranged in such a way that a surface wave can be generated in a direction tangential to this round region. A centrifuge can be generated in this way.
In a further development of the process according to the invention, the quantity of matter is analyzed inside at least one region of the solid-body surface with respect to a physical, chemical, or biological characteristics. This can take place during the application of the surface wave to generate a movement, or the process according to the invention can be used to transport the quantity of matter to an analysis station.
A process designed in this manner offers the advantage that both the movement and the analysis of the quantity of matter are possible on one xe2x80x9cchip.xe2x80x9d
For example, the at least one quantity of matter can be separated from the rest of the quantity of matter, either before or after the analysis, e.g. by irradiation of a surface wave.
A separation can also be achieved with a single surface wave. If a surface wave is sent to a small quantity of matter, e.g. a quantity of liquid, then the quantity of matter is placed in motion by transfer of an impulse to a part of the total quantity of matter, because of the surface tension and the incompressibility of the liquid. If, however, a surface wave is selected with a strength whose impulse can overcome the surface tension, then a part of the quantity of matter can be separated and moved forward by the impulse transfer from the surface wave.
Finally, a protecting layer can be applied to a device according to the invention, the thickness of which is less than the typical penetration depth of a surface wave. Such a protective layer is important when materials should be manipulated that would be damaged on the piezoelectric substrate used or the piezoelectric region of the substrate. Thus, e.g., a biological molecule would be damaged on a piezoelectric substrate of gallium arsenide. If the layer is thinner than the typical penetration depth of a surface wave, i.e. about a wavelength, then the functionality of the piezoelectric surface does not suffer or suffers only a little by the application of a protective layer. Alternatively, a substrate can be used of a material with a desired surface chemistry, even if this material is not piezoelectric. Then the surface is coated in the desired regions with a piezoelectric material, e.g. zinc oxide. In this case, it may be sufficient, e.g. when an electric-stimulation mechanism is used, to apply the piezoelectric coating material only in the region of the surface in which the surface-wave generating direction is located. There, the surface wave is then generated by the piezoelectric effect, and it cannot move forward in the non-piezoelectric substrate.
Finally, a piezoelectric coating can also be used in selected regions of the surface to modulate the wetting properties.
A protective layer can be made e.g. of quartz. Such a quartz layer is harmless, e.g. for biological molecules.
Analysis of e.g. size, masse, optical, magnetic, electric, and/or dielectric properties can likewise by performed with the aid of surface waves. In addition, the quantity of matter can be irradiated with a surface wave and the effect of the quantity of matter on the surface wave can be studied.
It is likewise possible that the quantity of matter can be modified in at least one region of the solid-body surface in which it applied, e.g. with the aid of surface waves, by chemical, physical, or biological processes. This can be achieved e.g. with appropriate functionalizing of a region of the solid-body surface in regard to physical, chemical, or biological properties.
It is especially advantageous for the quantity of matter to be immobilized reversibly and temporarily on at least one region of the solid-body surface, by modulation or coating of this region, for analysis purposes or modification purposes, by chemisorption or physisorption. This is achieved, e.g., by an appropriate functionalization of the solid-body surface, when e.g. it is rougher than the surroundings or has different wetting properties.
The process according to the invention can also be used to bring at least two quantities of matter into contact in at least one region of the solid-body surface by specific or directed movement for the purpose of at least one physical, chemical, biological reaction. This special embodiment of the process according to the invention makes possible a reaction between very small quantities of matter. Acoustic surface waves are used to transport the individual quantities of matter toward each other, bring them into contact, and possibly to mix them. If necessary, surface waves can then be used to strengthen or stop the reaction between the two quantities of matter used.
In an embodiment of the process according to the invention, an external supply reservoir or an external receiving reservoir can be connected with the aid of a defined trajectory on the device, in order to transport the quantity of matter into the device or out of the device.
A supply reservoir or a receiving reservoir can also be provided on the solid-body surface itself, in order to deliver or collect the quantity of matter.
Such a reservoir can be formed by appropriate functionalization of the surface, e.g. by lithographically defined grooves or barriers. It is likewise conceivable to change a solid-body surface in its wetting properties so that the quantity of matter stays in it preferentially. An appropriate modulation of the wetting properties can be generated in a similar manner as modulation of the wetting properties is achieved for the embodiment with defined trajectories.
In one embodiment of the process according to the invention, a region of the solid-body surface is provided with a device for local warming. Such a device makes it possible for a quantity of matter to be moved with the aid of acoustic surfaces* to or through a heated region, in order, e.g. to promote a reaction.
The device according to the invention or the process according to the invention can be used wherever small quantities of matter should be moved or manipulated on a solid-body surface. This is conceivable in liquids, gases, solid bodies, or combinations, mixtures, and/or dispersions. The process according to the invention or the device according to the invention can be used advantageously for analysis, synthesis, separation, mixing, proportioning, or centrifuging of a small quantity of matter.